The overall scientific goal of the Clinical and Experimental Therapeutics Program is to develop and test novel and, where possible, mechanistically oriented and gene-directed therapeutic approaches to patients with solid tumors. This Program is based on the assumption that the major solid tumors in man are, for the most part, inherently resistant to chemo- and radiation therapy or are capable of rapidly acquiring resistance to these modalities of treatment. Thus, the focus of the program is on the inherent and acquired resistance of solid tumors to chemotherapy and radiation therapy in patients with primary, local-regional, or disseminated disease. The specific aims of the overall program are: (a) to investigate basic pharmacologic mechanisms of action and resistance both in vitro and in patient materials to agents that interact with or alter critical molecular targets for antineoplastic therapy; (b) to apply innovative gonetargeted, pharmacokinetic, and pharmacodynamic-principles to solid tumor experimental therapeutics; and (c) to develop novel multidisciplinary radiation, surgical, and chemoradioimmunotherapeutic approaches to improving both localregional and systemic control in patients with solid tumors. The Program has three major subdivisions: Molecular Pharmacology and Pre-Clinical Experimental Therapeutics; Clinical Pharmacology and Developmental Therapeutics; and Multimodality Treatment of Solid Tumors. The elements of this Program are highly interactive and allow the Cancer Center to pursue complex multidisciplinary and combined laboratory and clinical investigations. Members of all elements of the Program meet regularly and collaborate extensively on peer-reviewed, funded translational research projects that have brought several novel therapeutic approaches from City of Hope laboratories to the clinic. The Program is led by Dr. James Doroshow whose interests in molecular and clinical cancer pharmacology and translational oncologic experimental therapeutics have helped to stimulate the development of a laboratory-based approach to the evaluation of new anticancer agents. The Program brings added value to its membership in the form of Program meetings, the establishment of new shared facilities, and structured research training activities that focus the membership on its shared goal of collaborating both intra- and interprogrammatically to develop novel approaches to solid tumor therapy. The 21 Full and 20 Associate Members of the program have published over 422 articles, books, book chapters, etc., from 1996-2001. Of these, 128 are intraprogrammatic, 73 are interprogrammatic, and 27 represent both inter- and intraprogrammatic publications.